Oncological and functional results of robotic salvage radical prostatectomy after permanent brachytherapy implants.

PURPOSE: To evaluate the feasibility of robotic salvage prostatectomy for local recurrence after permanent brachytherapy implants for prostate cancer. PATIENTS AND METHODS: Seven patients were operated by robotic salvage prostatectomy with or without pelvic lymph node dissection between October 2007 and March 2012, for a local recurrence after iodine 125 permanent brachytherapy implants. Local recurrence was proved by prostate biopsies, once biochemical relapse was diagnosed and imaging assessment performed. RESULTS: The average age of a patient at the time of diagnosis was 66 years (62-71 years). The median nadir prostate specific antigen (PSA) serum concentration after brachytherapy was 1.29ng/mL (0.6-2.1ng/mL), obtained after a median of 12 months (7-21 months). The average [PSA] before robotic salvage prostatectomy was 6.60ng/mL (4.17-13.80ng/mL). [PSA] at 1 and 3 months after prostatectomy was less than 0.05ng/mL in five patients. [PSA] remained below 0.05ng/mL for six patients at 12 and 24 months. One month after robotic salvage prostatectomy, all patients had at least partial urinary incontinence. At 12 and 24 months after robotic salvage prostatectomy four patients have regained full urinary continence. In terms of erectile function at 24 months, three patients retained erectile function with possible sexual intercourse. CONCLUSION: Robotic salvage prostatectomy appears to be a reliable treatment in terms of oncological outcome with convincing results both for urinary continence and erectile function for selected patients with local recurrence after permanent brachytherapy implants.

[Adjuvant radiotherapy for bladder cancer in patients with risk of locoregional recurrence: Who, what and how?] / Radiothérapie adjuvante des tumeurs de vessie à risque de rechute locorégionale : pour qui, pourquoi et comment ?

Radical cystectomy with extended pelvic lymph node dissection remains the standard of care for non-metastatic muscle-invasive bladder cancer. Locoregional control is a key factor in the outcome of patients since it is related to overall survival, metastasis-free survival and specific survival. Locoregional recurrence rate is directly correlated to pathological results and the quality of lymphadenectomy. In addition, while pre- or postoperative chemotherapy improved overall survival, it showed no impact on locoregional recurrence-free survival. Several recent publications have led to the development of a nomogram that predicts the risk of locoregional recurrence, in order to identify patients for which adjuvant radiotherapy could be beneficial. International cooperative groups have then come together to provide the rational for adjuvant radiotherapy, reinforced by recent technical developments limiting toxicity, and to develop prospective studies to reduce the risk of relapse. The aim of this critical literature review is to provide an overview of the elements in favor of adjuvant radiation for patients treated for muscle-invasive bladder cancer.

[Treatments around surgery of prostate cancer and surgery of recurrence]. / Traitements complémentaires de la chirurgie du cancer de la prostate et chirurgie de la récidive.

OBJECTIVE: To describe neoadjuvant and adjuvant treatments to surgery and the place of surgery in the recurrence after primary treatments. MATERIAL AND METHOD: Bibliography search was performed from the database Medline (National Library of Medicine, Pubmed), selected according to the scientific relevance. The research was focused on treatments before and after surgery, biological recurrence and surgery as the procedure in case of failure of other treatments of non-metastatic prostate cancer. RESULTS: Main oncological objectif of surgery is to decrease positive surgical margins by good adequation between technics and tumor and patient status. Neoadjuvant treatments are today disappointing; however, adjuvant radiotherapy and hormonotherapy demonstrated their interest in case of extracapsular extension, positive margins or invasion of lymph nodes. Nevertheless, superiority of adjuvant treatment to salvage treatment is still debated. Radical prostatectomy is still the only curative treatment in case of failure of another localized treatment. CONCLUSION: Radical prostatectomy has to be one of the main references of localized prostate cancer treatments especially in case of multimodal approach. Pathological exam of specimen and postoperative PSA value should precise the optimal management of prostate cancer.

Novel insights into nickel import in Staphylococcus aureus: the positive role of free histidine and structural characterization of a new thiazolidine-type nickel chelator.

Staphylococcus aureus possesses two canonical ABC-importers dedicated to nickel acquisition: the NikABCDE and the CntABCDF systems, active under different growth conditions. This study reports on the extracytoplasmic nickel-binding components SaNikA and SaCntA. We showed by protein crystallography that SaNikA is able to bind either a Ni-(l-His)2 complex or a Ni-(l-His) (2-methyl-thiazolidine dicarboxylate) complex, depending on their availability in culture supernatants. Native mass spectrometry experiments on SaCntA revealed that it binds the Ni(ii) ion via a different histidine-dependent chelator but it cannot bind Ni-(l-His)2. In vitro experiments are consistent with in vivo nickel content measurements that showed that l-histidine has a high positive impact on nickel import via the Cnt system. These results suggest that although both systems may require free histidine, they use different strategies to import nickel.

[Imagery of treated prostate cancer]. / Imagerie post-thérapeutique du cancer de la prostate.

INTRODUCTION: Diagnosis, localization of recurrence in the management of prostate cancer patients with increasing concentrations of tumor serum markers is crucial for treatment planning of the patients. The present review describes the role of prostate MRI and (18) Fcholine PET/computed tomography (CT) in tumor detection and extent, when there is a suspicion of residual or recurrent disease after treatment of prostate cancer. METHOD: A systematic review of the literature was performed by searching in the PUB MED/MEDLINE database searching for articles in French or English published between the last 12years. RESULTS: In patient with a clinical suspicion of recurrence after treatment for prostate cancer, imaging can be used to distinguish between local recurrence and metastatic disease. (11)C-choline PET/CT and pelvic multiparametric MR imaging (mp MRI) are complementary in this indication. In this paper, the current status of imaging techniques used for the staging of patients with suspected locally recurrent or metastatic disease in patients treated for prostate cancer were reviewed. CONCLUSION: Mp MRI of the prostate may be valuable imaging modality for the detection and localization of local recurrence. C-choline PET/CT offers an advantage in detecting metastatic disease to lymph node and bone.

[Management of low-risk prostate cancer]. / Prise en charge des tumeurs de la prostate à faible risque évolutif.

INTRODUCTION: The widespread use of prostate cancer screening has led to a stage migration resulting in an increase in the diagnosis of low-risk disease, which currently accounts for 40-50% of diagnosed forms. New therapeutic strategies have been developed in order to minimize the risk of overtreatment. METHODS: A systematic review of the literature over the past 20 years was performed using the Medline database. The literature selection was based on evidence and practical considerations. RESULTS: Low-risk tumors are conventionally defined by the d'Amico classification. The use of multiparametric MRI helps to better characterize these tumors. The contribution of molecular biology remains to be determined in clinical practice. Novel therapeutic options for low-risk disease are currently being evaluated. CONCLUSION: The new therapeutic strategies are evolving. They seek to reduce overtreatment without compromising oncological success.

[Postoperative radiotherapy of prostate cancer]. / Radiothérapie postopératoire des cancers de la prostate.

Between 10 and 40% of patients who have undergone a radical prostatectomy may have a biologic recurrence. Local or distant failure represents the possible patterns of relapse. Patients at high-risk for local relapse have extraprostatic disease, positive surgical margins or seminal vesicles infiltration or high Gleason score at pathology. Three phase-III randomized clinical trials have shown that, for these patients, adjuvant irradiation reduces the risk of tumoral progression without higher toxicity. Salvage radiotherapy for late relapse allows a disease control in 60-70% of the cases. Several research in order to improve the therapeutic ratio of the radiotherapy after prostatectomy are evaluate in the French Groupe d'Étude des Tumeurs Urogénitales (Gétug) and of the French association of urology (Afu). The Gétug-Afu 17 trial will provide answers to the question of the optimal moment for postoperative radiotherapy for pT3-4 R1 pN0 Nx patients, with the objective of comparing an immediate treatment to a differed early treatment initiated at biological recurrence. The Gétug-Afu 22 questions the place of a short hormonetherapy combined with image-guided, intensity-modulated radiotherapy (IMRT) in adjuvant situation for a detectable prostate specific antigen (PSA). The implementation of a multicenter quality control within the Gétug-Afu in order to harmonize a modern postoperative radiotherapy will allow the development of a dose escalation IMRT after surgery.

[Prostate cancer surgical margin: review by the CCAFU (Oncology Committee of the French Association of Urology)]. / Les marges chirurgicales dans le cancer de la prostate. CCAFU revue de la littérature.

OBJECTIVE: Literature showed the impact of surgical margin status on prognosis after radical prostatectomy (mostly on biochemical survival). Margin status is an easy self-evaluation of surgical practice to assess. The aim of this paper was to define what a positive surgical margin (PSM) is and how to prevent the occurrence, to precise the impact on survival and how to treat. METHOD: A literature analysis with Pubmed has been performed to 2012, furthermore conclusions of the main congresses with selection committee and review publication have also been studied. RESULTS: PSM is defined as "tumor cells touching the ink on the specimen edge". The most frequent reported incidence is between 15 to 20%. Margin status remains one of the major criteria to determine the need of adjuvant radiotherapy after surgery. Quality of life is not or only lightly modified by radiotherapy with the current techniques. Adjuvant radiotherapy improves biological survival but is synonymous with overtreatment in many times. Salvage radiotherapy has to be quickly performed after Prostate Specific Antigen (PSA) relapse (PSA<1 ng/mL even<0.5 ng/mL). CONCLUSION: This literature review did not allow to suggest superiority of one surgical technique over another. In the same way, the kind of dissection i.e. bladder neck or neurovascular bundle preservation does no clearly modify PSM rate. However, it seems logical to "customize" dissection according to prostate cancer characteristics (D'Amico criteria for instance) guided with multiparametric MRI. Intrafascial dissection has to be applied only to low risk. Lastly, the debate between adjuvant or salvage radiotherapy is always ongoing.

Characterization of prostate neuroendocrine cancers and therapeutic management: a literature review.

OBJECTIVES: Neuroendocrine prostate cancers (NEPCs) are rare. The current lack of consensus for clinical, biological and pathological characterization as well as therapeutic approach makes the management of those tumors a clinical challenge. This literature review aims to summarize available data on the characterization and management of patients with prostate cancer with a neuroendocrine element. We try to identify major controversies and uncertainties in order to understand all aspects of this particular entity. METHODS: We searched for all articles published and registered in the MEDLINE database before 31 November 2013 with the following search terms: (('prostatic neoplasms' (MeSH Terms)) AND ('carcinoma, neuroendocrine' (MeSH Terms)) OR ('carcinoma, small cell' (MeSH Terms))) AND (English (Language)). RESULTS: Case reports, letters or comments were excluded. We then selected relevant articles from titles and abstracts. Overall, 278 articles published between 1976 and November 2013 were identified. No definition of NEPC seems to be clearly established. Natural history of the disease reveals poor prognosis with median survival of up to 10 to 13 months. Histological characterization appears difficult. Serum markers could be helpful with some controversies in terms of prognostic significance. Concerning management, the majority of patients received local treatment combined with chemotherapy in case of early and localized disease. Few clinical trials described strategy for metastatic disease. CONCLUSIONS: The exploration of the different pathways implicated in the neuroendocrine differentiation of prostate cancers is essential for the comprehension of castration-resistance mechanisms. It will enable the identification of optimal therapeutic strategies for which no recommendation is currently established. Inclusion in prospective clinical trials appears necessary to identify the adequate strategy.

[Radiotherapy after testicular-sparing surgery for bilateral or monorchide testicular tumours: an innovative approach]. / Radiothérapie testiculaire après chirurgie conservatrice des tumeurs germinales bilatérales ou sur testicule unique: une stratégie innovante.

Testicular-sparing surgery may avoid definitive testosterone supplementation and preserve fertility in selected cases of men presenting with bilateral testicular tumours or in case of monorchidia. Testicular-sparing surgery may enable the conservation of both endocrine function and spermatogenesis in selected young men in order to preserve natural fatherhood, avoid definitive androgen replacement therapy and probably improve quality of life by reducing psychosexual consequences of anorchia. The tumorectomy must be followed by an external irradiation of the remaining testicle to eradicate testicular intratubular neoplasia revealed in 82% of cases after per-surgery biopsy. This approach concerns some rare indications. Dose level and technical consideration are still debated.

[Prostate brachytherapy: indications and outcomes]. / Curiethérapie exclusive du cancer de la prostate par implants permanents : indications et résultats. Revue du CC-AFU.

INTRODUCTION: To summarize the indications and outcomes of low dose-rate prostate brachytherapy with permanent implants. METHODS: Bibliographic database PubMed was searched with prostate cancer and brachytherapy as keywords from 1995 to 2012. RESULTS: The main indication of prostate brachytherapy is the favorable group, but it could be proposed to patients with an intermediate prognostic group if the PSA is ≤ 15 ng/mL or if the Gleason score is 7 (3+4), under cover of a prostate MRI without any extra-capsular extension. Oncologic results are similar to those of surgery or external beam irradiation (EBRT), with a 10-yr biochemical control rate approaching 90%. Urinary toxicity is common during the year following the implant, mainly irritative symptoms; 5 to 15% of patients experienced acute urinary retention. A prostate volume higher than 50 cc or an initial high international prostatic symptom score (IPSS) are predictive of toxicity and are recognized as relative contraindications of the technique. Sexual activity is maintained in 60% of patients. CONCLUSION: Brachytherapy must be proposed as a validated option beside active surveillance, surgery and EBRT.

[CCAFU Recommendations 2013: Diagnosis, treatment, follow up of urological cancers]. / Recommandations de bonnes pratiques cliniques 2013 du CCAFU: Diagnostic, traitement et suivi des cancers urologiques chez l'homme et la femme.

INTRODUCTION: The objective of the 2013 recommendations performed by the different committees of CCAFU is to improve the management of urological cancers regarding diagnosis, clinical assessment and treatments in men and women. MATERIAL AND METHODS: 2010 clinical guidelines were updated based on international AUA and EAU guidelines and on systematic literature search performed by each sub-Committee in Medline and PubMed databases to evaluate references, levels of evidence and grade of recommendation. RESULTS: CCAFU clinical guidelines reply to the main clinical questions on management of urological cancers. CONCLUSION: French clinical guidelines are updated every three years by CCAFU in accordance with the main international guidelines in onco-urology.

[Incidence and mortality of urological cancers in 2012 in France]. / Projection de l'incidence et de la mortalité par cancer urologique en France en 2012.

OBJECTIVES: Present national estimations of the incidence and mortality trends in urological cancers in France between 1980 and 2012. MATERIAL AND METHODS: Francim database and French Register of Cancers. RESULTS: Analysis of the current data shows a regular increase of the incidence of renal cancer in men and women (7,781 cases in men and 3,792 in women in 2012). For bladder cancer, trends are divergent. There is a small reduction in incidence for men and an increase for women (9,549 cases in men and 2,416 in women in 2012). Testicular cancer is still increasing slightly (2,317 incidental cases in 2012). The incidence of prostate cancer experienced a huge increase up until 2005, and thereafter it decreased sharply, though it is difficult to discern whether this drop (which was observed up until 2008) continued at the same rate after that point (56,841 incidences in 2012 based on the rates calculated for 2009). CONCLUSION: The analyses by organ database show that there are significant variations in the incidence of urological cancers, particularly for prostate cancer, which shows that both the natural history of urological tumours and the methods of detection have an impact on incidence.

[CCAFU Recommendations 2013: Prostate cancer]. / Recommandations en onco-urologie 2013 du CCAFU : Cancer de la prostate.

INTRODUCTION: The sub Comittee prostate of the CCAFU established guidelines for diagnostic, treatment, evaluation and standart of care of prostate cancer. METHODS: Guidelines 2010 were updated based on systematic literature search performed by the sub-Comittee in Medline and PubMed databases to evaluate references, levels of evidence and grade of recommandation. RESULTS: Pathological examination of the tissue specimens was defined specifically for Gleason score according to ISP 2005 recommandations. Prostate and pelvis RMN became the reference in terms of radiological exam. Individual and early diagnosis of prostate cancer was defined and role of PSA was precised. Active surveillance became one of the standart of care of low-risk tumors, radical prostatectomy remained one of the options for all risk group tumors, length of hormonotherapy in association with radiotherapy was precised according to the risk group. Side effects of hormonotherapy treament needed specific supervision ; hormonotherapy had no indication in case of non metastatic tumors and intermittent hormonotherapy in metastatic tumors. New hormonal drugs in pre and post chemotherapy and bone target drugs opened new therapeutics pathways. CONCLUSION: From 2010 to 2013, standarts of care of prostate cancer were modified because of results of prospective studies and new therapeutics. They allowed precise treatments for each specific clinical situation. In the future, multidisciplinary treatments for high risk tumors, time of adjuvant treatment and sequencies of new hormonal treatment had to be defined.

[5 alpha-reductase inhibitors and prostate cancer: a statement of the Committee of Cancerology of the French Association of Urology]. / Inhibiteurs des 5 alpha-réductases et cancer de la prostate : une mise au point du Comité de cancérologie de l'Association française d'urologie.

INTRODUCTION: Two randomised trials and negative conclusion of the FDA about inhibitors of 5 alpha-reductase in prevention of prostate cancer need a revision of the indications of these drugs. METHODS: After description of fundamentals data, review of the literature in PubMed library was performed to analyse the indications of these drugs according to the different stages of prostate cancer. RESULTS: Even if PCPT and REDUCE studies showed a decrease of cancers with the use of 5 alpha-reductase (5ARI) but with side effects, there is no indication for prostate cancer prevention by these drugs. In the same way, despite the results of REEDEM study, there is no indication of these drugs in active surveillance. CONCLUSION: Despite the large interest of these drugs, no recommendation can be given for indications of 5ARI in prevention or treatment of prostate cancer.

[Hodgkin's disease and breast cancer: for which patients is there an association? A series from Institut Bergonié]. / Maladie de Hodgkin et cancer du sein: une association pour quelles patientes ? À propos d'une série de l'institut Bergonié

OBJECTIVE: Breast cancer is the most frequent secondary tumor for women treated for Hodgkin's disease. It is important to study the risk factors associated to be able to adapt the monitoring of these women. PATIENTS AND METHODS: This is a retrospective study from Institut Bergonié, a comprehensive French Cancer Center, concerning the women treated for Hodgkin's disease and having developed a breast cancer. RESULTS: Among 328 women treated for Hodgkin's disease between January 1968 and December 1994, 20 patients developed 25 breast cancers. The average age of the patients during the irradiation was 24 years and the average period of occurrence of the cancer was 19 years. An irradiation of the chest wall and an under-diaphragmatic irradiation in doses of 40Gy are risk factors for the occurrence of breast cancer. A young age, less than 30, in the treatment of Hodgkin's disease tend to be significant. DISCUSSION AND CONCLUSION: This population of women with a high risk of breast cancer thus has to benefit from an appropriate monitoring program, which is what we suggest setting up in the Institut Bergonié.

[High-risk prostate cancer. Review by the Oncology Committee of the French Urology Association]. / Cancer de la prostate à haut risque de progression. Article de revue du comité de cancérologie de l'association française d'urologie.

INTRODUCTION: Localized prostate tumors have various clinical, biological and histopathological characteristics that lead to different progression profiles. High-risk prostate cancer has been classically defined by clinical examination, PSA levels and histopathological data. High-risk prostate cancer has usually a worse outcome, but classic stratification predictive of outcome for prostate cancer is a matter of debate concerning its accuracy. METHODS: A systematic review of the literature on high-risk prostate cancer over the 15 last years was carried out on Medline database. The literature selection was based on evidence and practical considerations. RESULTS: A great deal of scientific work have been deployed to prove that high-risk prostate cancer should be approached by teamwork including radio-hormone therapy, systemic treatment with long term use of LH-RH and a radical prostatectomy with adequate lymph node dissection. Selection of patients is essential to define individualized therapeutic strategy and timing for every modality should come as a consensus of medical supported evidence. CONCLUSION: Accurate patient selection and multimodal treatment offer the best therapeutic option in high-risk prostate cancer.